Colon cancer is a leading cause of morbidity and death in Americans. There is increasing evidence that bacterially-induced inflammation increases risk of intestinal cancer. We have recently developed a novel lymphocyte-deficient mouse model of microbially induced carcinoma that resembles colon cancer in humans. The invasive colon cancer that develops in this mouse model is treatable using CD4+CD25+ regulatory lymphocytes. We propose to use this rapidly inducible cancer platform of colitis-associated cancer to investigate how CD4+CD25+ regulatory cells are able to treat colon cancer. We have also recently found that CD4+CD25+ cells induce regression of intestinal tumors in the ApcMin/+ mouse model of colorectal cancer. We propose to apply this widely used cancer platform to investigate how CD4+CD25+ are able to treat colorectal cancer not so clearly linked with intestinal inflammation. We speculate that regulatory cells work by delivering IL10 to down-modulate inflammation that sustains cancer. We aim to probe inflammatory and neoplastic events to identify targets to disrupt neoplastic invasion. Information gained from these studies may elucidate pivotal mechanisms and uncover novel strategies for prevention and treatment of human colon cancer.